Federal Register / Vol. 63, No. 119 / Monday, June 22, 1998 / Notices 33937

Institutes of Health (NIH) has submitted

to the Office of Management and Budget

(OMB) a request to review and approve

the information collection listed below.

This proposed information collection

was previously published in the Federal

Register on March 26, 1998, page 14721

and allowed 60 days for public

comment. No public comments were

received. The purpose of this notice is

to allow an additional 30 days for public

comment. The National Institutes of

Health may not conduct or sponsor, and

the respondent is not required to

respond to, an information collection

that has been extended, revised or

implemented on or after October 1,

1995, unless it displays a currently valid

OMB control number.

Proposed Collection: Title: American

Stop Smoking Intervention Study for

Cancer Prevention (ASSIST) Final

Evaluation: ‘‘Tobacco use Supplement

to the 1998–1999 Current Population

Survey’’. Type of Information Request:

OMB #0925–0368, Exp. 3/31/97,

REINSTATEMENT, with change. Need

and Use of Information Collection: The

‘‘Tobacco use’’ supplement to the

Current Population Survey conducted

by the Bureau of the Census will collect

data from the civilian noninstitutionalized population on tobacco

use and smoking prevalence, smoking

intervention dissemination of workplace

smoking policies and cessation

programs, and changes in smoking

norms and attitudes. The data will be

used by the National Cancer Institute to

evaluate the effectiveness of the

American Stop Smoking Intervention

Study for Cancer Prevention (ASSIST),

a large scale, 17-state demonstration

project. This survey will also provide

valuable information to Government

agencies and to the general public

necessary for tobacco control research.

The survey will allow state specific

estimates to be made. Data will be

collected in September 1988, January

1999 and May 1999 from approximately

255,000 respondents. Frequency of

Response: One-time study. Affected

Public: Individuals or households. Type

of Respondents: Persons 15 yrs of age or

older. The annual reporting burden is as

follows: Estimated Number of

Respondents: 170,000; Estimated

Number of Responses per Respondent:

1; Average Burden Hours per Response:

.1169; and Estimated Total Annual

Burden Hours Requested: 19,873. The

annualized cost to respondents is

estimated at: $198,727. There are no

Capital Costs, Operating Costs, and/or

Maintenance Costs to report.

Request for comments: Written

comments and/or suggestions from the

public and affected agencies should

address one or more of the following

points: (1) Evaluate whether the

proposed collection of information is

necessary for the proper performance of

the function of the agency, including

whether the information will have

practical utility; (2) The accuracy of the

agency’s estimate of the burden of the

proposed collection of information,

including the validity of the

methodology and assumptions used; (3)

Enhance the quality, utility and clarity

of the information to be collected; and

(4) Minimize the burden of the

collection of information on those who

are to respond, including the use of

appropriate automated, electronic,

mechanical, or other technological

collection techniques or other forms on

information technology.

Direct Comments to OMB: Written

comments and/or suggestions regarding

the item(s) contained in this notice,

especially regarding the estimated

public burden and associated response

time, should be directed to the: Office

of Management and Budget, Office of

Regulatory Affairs, New Executive

Office Building, Room 10235,

Washington, DC 20503, Attention: desk

Officer for NIH. To request more

information on the proposed project or

to obtain a copy of the data collection

plans and instruments, contact Anne

Hartman, Statistician, National Cancer

Institute, Executive Plaza North, Room

313, Bethesda, Maryland 20892–7344,

or call non-toll free number (301) 496–

4970, or FAX your request to (301) 435–

3710, or E-mail your request, including

your address, to ah42t@nih.gov or

AnnelHartman@nih.gov.

Comments due date: Comments

regarding this information collection are

best assured of having their full effect if

received on or before July 22, 1998.

Dated June 11, 1998.

Reesa L. Nichols,

NCI Project Clearance Liaison.

[FR Doc. 98–16428 Filed 6–19–98; 8:45 am]

BILLING CODE 4140–01–M

DEPARTMENT OF HEALTH AND

HUMAN SERVICES

National Institutes of Health

Licensing Opportunity and/or

Cooperative Research and

Development Agreement (‘‘CRADA’’)

Opportunity: Drug and Method To

Prevent and Treat Graft-Versus-Host

Disease and Allograft Rejection

AGENCY: National Institutes of Health,

PHS, DHHS.

ACTION: Notice.

SUMMARY: The NIH is seeking Licensees

to further develop, evaluate, and

commercialize anti-Tac(Fv)–PE38, also

known as LMB2. Anti-Tac(Fv)–PE38 is

a recombinant toxin composed of the Fv

portion of the anti-Tac antibody which

binds to the a subunit of the IL2

receptor (also called P55, Tac, or CD25)

fused to PE38 a mutant form of

Pseudomonas Exotoxin A. Anti-Tac

(Fv)–PE38 is very cytotoxic to normal or

malignant cells expressing IL2 receptors

and is being developed for several

proposed applications including (1.) the

prevention of Graft-versus Host Disease

(‘‘GVHD’’) by purging bone marrow of

potentially recipient-reactive donor Tcells, (2.) the treatment of Graft-versus

Host Disease by i.v. administration, and

(3.) the treatment or prevention of

allograft rejection. The goal is to move

this methodology into clinical trials.

The inventions claimed in USPN

4,892,8927, Entitled: ‘‘Recombinant

Pseudomonas Exotoxins: Construction

of an Active Immunotoxin with Low

Side Effects’’; USSN 07/865,722,

Entitled: ‘‘Recombinant Antibody-Toxin

Fusion Protein’’; USPN 5,696,237,

Entitled: ‘‘Recombinant Antibody-Toxin

Fusion Protein’’; and USSN 08/461,825,

Entitled: ‘‘Recombinant Antibody-Toxin

Fusion Protein’’; are available for either

exclusive or nonexclusive licensing for

these aforementioned applications (in

accordance with 35 U.S.C. 207 and 37

CFR Part 404).

DATES: Respondees interested in

licensing the invention(s) will be

required to submit an ‘‘Application for

License to Public Health Service

Inventions’’ on or before September 21,

1998 for priority consideration.

Interested CRADA collaborators must

submit a confidential proposal summary

to the NCI on or before September 21,

1998 for consideration. Guidelines for

preparing full CRADA proposals will be

communicated shortly thereafter to all

respondents with whom initial

confidential discussions will have

established sufficient mutual interest.

CRADA proposals submitted thereafter

may be considered if a suitable CRADA

Collaborator has not been selected.

ADDRESSES: Questions about licensing

opportunities may be addressed to J.R.

Dixon, Ph.D., Technology Licensing

Specialist, Office of Technology

Transfer, National Institutes of Health,

6011 Executive Boulevard, Suite 325,

Rockville, Maryland 20852–3804;

Telephone: (301) 496–7056 ext. 206;

Facsimile: (301) 402–0220; E-Mail:

‘‘DixonJ@OD.NIH.GOV’’. Information

about Patent Applications and pertinent

information not yet publicly described
33938 Federal Register / Vol. 63, No. 119 / Monday, June 22, 1998 / Notices

can be obtained under the terms of a

Confidential Disclosure Agreement.

Depending upon the mutual interests

of the Licensee(s) and the NCI, a

Cooperative Research and Development

Agreement (CRADA) to collaborate to

improve the properties of the Anti-Tac

(Fv)-PE38 may also be negotiated.

Proposals and questions about this

CRADA opportunity may be addressed

to Ms. Karen Maurey, Acting Deputy

Director, Technology Development &

Commercialization Branch, National

Cancer Institute, 6120 Executive

Boulevard, Room 450, Rockville,

Maryland 20852; Telephone: (301) 496–

0477; Facsimile: (301) 402–2117.

Respondees interested in submitting a

CRADA. Proposal should be aware that

it may be necessary to secure a license

to the above mentioned patent rights in

order to commercialize products arising

from a CRADA.

SUPPLEMENTARY INFORMATION: Bone

marrow transplantation (‘‘BMT’’) is an

useful therapy for the treatment of

various malignant and nonmalignant

genetic and acquired blood disorders

which are otherwise incurable.

However, a significant limitation of

using allogeneic BMT is that only a

minority (less than 30%) of patients

have an HLA-identical sibling donor.

The use of phenotypically matched

unrelated donors can only partially

overcome this problem, mainly because

the time needed to search for an

acceptable donor is often too long for

patients with advanced disease. Another

problem is that ethnic or racial

minorities are under-represented in the

volunteer bone marrow donor registries.

As a result, the chances of finding an

unrelated matched donor for such

patients is limited.

Graft-versus-Host disease is one of the

most frequent complications of

allogenic BMT, and is particularly

difficult to control in the mismatched

setting. Not only does severe GVHD

impact greatly on the quality of life of

the transplant recipient, as well as

contribute significantly to the cost of

therapy, but it is the major cause of

patient mortality either directly or

indirectly (e.g. opportunistic infections

due to long-term immunosuppressive

therapy).

As has been well documented, GVHD

is the result of alloreactive T-cells in the

bone marrow graft that are capable of

recognizing and attacking the tissues of

the immunosuppressed recipient. As it

also known, upon recognition and

activation by foreign antigen, T-cells

express the receptor for interleukine 2

(‘‘LL–2)—which offers a possible

method for the removal of alloreactive

T-cells. If it were possible to eliminate

the presence of contaminating recipientalloreactive T-cells in the bone marrow

graft, thus preventing or reducing the

severity of GVHD, allogeneic

transplantation might find greater

applications and use in the treatment of

a variety of other diseases (e.g.,

autoimmune diseases such as

rheumatoid arthritis, etc.). In cases

where haploidentical related donors

may be readily available to serve as a

donor, specific T-cell depletion would

permit the haploidentical donor’s

immunity to be transferred with the

graft while preventing severe GVHD,

thus improving the overall patient

outcome

While GVHD can be prevented by

extensive non-selective T-cell depletion

of the bone marrow graft, this procedure

increases the risk of infection and graft

rejections. In HLA genotypically

identical sibling transplant, GVHD can

be controlled somewhat through the use

of immunosuppressive therapy (e.g.,

Cyclosporin, Methotrexate, etc.).

However, such therapeutic modalities

are much less effective in the

mismatched setting and are associated

with susceptibility to bacteria and viral

infections, development of new

malignancies, and end organ failure.

NIH/NCI scientists at the National

Cancer Institute have developed and

evaluated in animal models, a

recombinant immunotoxin (e.g., AntiTac (Fv)/PE38) which kills activated Tcells at very low immunotoxin

concentrations. The subject

Immunotoxin is a single chain protein

composed of the Fv portion of an

antibody fused to the amino terminus of

the PE. The toxin has three domains: IA

is responsible for cell binding, II is

required for translocation and has the

proteolytic processing site, and III has

the ADP-ribosylating activity. After call

internalization, a truncated form of PE,

generated by proteolytic cleavage

translocates to the cytosol where ADPribosylation of elongation factor 2

terminates protein synthesis causing

cell death.

NIH/NCI scientists have shown that

Anti-Tac(Fv)–PE38 may prevent and

reduce the severity of GVHD by specific

elimination or reduction of recipientalloreactive donor T-cells without

adversely affecting other T-cell

population or compromising stem cell

engraftment and recipient

hematopoietic rescue and survival.

These experiments have demonstrated

that it is possible to inexpensively and

selectively eliminate or reduce the

numbers of alloreactive T-cells present

in a bone marrow graft resulting in

prevention of or a reduction in the

severity of GVHD after bone marrow

transplantation procedures, but does not

compromise stem cell engraftment and

recipient hematopoietic rescue and

survival. The methodology is simple

and does not involve significant lengths

of time or specialized equipment. Thus

it should be possible to transition these

findings to the clinical situation without

significant problems. If clinical results

approximate the observed animal

finding it might then be possible to

utilize BMT in many other disease

conditions.

In addition NIH/NCI scientists have

shown in a Phase I Trial that AntiTac(Fv)–PE38 can be safely

administered intravenously to patients

with cancer; good blood levels of the

immunotoxin are also achieved. Thus

Anti-Tac(Fv)–PE38 may also be used to

treat patients with GVHD or the treat

patients undergoing allograft rejection.

A Cooperative Research and

Development Agreement or CRADA

means the anticipated joint agreement to

be entered into by NCI pursuant to the

Federal Technology Transfer Act of

1986 and Executive Order 12591 of

April 10, 1987 as amended by the

National Technology Transfer

Advancement Act of 1995 to collaborate

to improve the properties of AntiTac(Fv)–PE38. The expected duration of

the CRADA would be from one (1) to

five (5) years.

The role of the NCI in the CRADA

may include, but not be limited to:

1. Providing intellectual, scientific,

and technical expertise and experience

to the research project.

2. Providing the Collaborator with

samples of the subject compounds to

create, optimize, test and develop

targeted drugs for clinical studies.

3. Planning research studies and

interpreting research results.

4. Carrying out research to improve

the properties of Anti-Tac(Fv)–PE38

which include, but are not restricted to,

increased production yield, decreased

side effects, increased cyotoxic activity

and better tissue penetration.

5. Publishing research results.

The role of the CRADA Collaborator

may include, but not be limited to:

1. Providing significant intellectual,

scientific, and technical expertise or

experience to the research project.

2. Planning research studies and

interpreting research results.

3. Providing samples of the subject

compounds to create, optimize, test and

develop targeted drugs for clinical

studies.

4. Providing technical and/or

financial support to facilitate scientific

goals and for further design of
Federal Register / Vol. 63, No. 119 / Monday, June 22, 1998 / Notices 33939

applications of the technology outlined

in the agreement.

5. Providing immunotoxin for

laboratory and animal studies.

6. Publishing research results.

Selection criteria for choosing the

CRADA Collaborator may include, but

not be limited to:

1. The ability to collaborate with NCI

on further research and development of

this technology. This ability can be

demonstrated through experience and

expertise in this or related areas of

technology indicating the ability to

contribute intellectually to ongoing

research and development.

2. The demonstration of adequate

resources to perform the research and

development of this technology (e.g.,

facilities, personnel and expertise) and

accomplish objectives according to an

appropriate timetable to be outlined in

the CRADA Collaborator’s proposal.

3. The willingness to commit best

effort and demonstrated resources to the

research and development of this

technology, as outlined in the CRADA

Collaborator’s proposal.

4. The demonstration of expertise in

the commercial development and

production of products related to this

area of technology.

5. The level of financial support the

CRADA Collaborator will provide for

CRADA-related Government activities.

6. The demonstration of expertise

pertinent to the development of models

to evaluate and improve the efficacy of

immunotoxin in the prevention or

treatment of graft-versus-host disease

and/or allograft rejection.

7. The willingness to cooperate with

the National Cancer Institute in the

timely publication of research results.

8. The agreement to be bound by the

appropriate DHHS regulations relating

to human subjects, and all PHS policies

relating to the use and care of laboratory

animals.

9. The willingness to accept the legal

provisions and language of the CRADA

with only minor modifications, if any.

These provisions govern the distribution

of patent rights to CRADA inventions.

Generally, the right of ownership are

retained by the organization that is the

employer of the inventor, with (1) the

grant of a license for research and other

Government purposes to the

Government when the CRADA

Collaborator’s employee is the sole

inventor, or (2) the grant for an option

to elect an exclusive or nonexclusive

license to the CRADA Collaborator

when the Government employee is the

sole inventor.

Dated: June 11, 1998.

Kathleeen Sybert,

Acting Director, Technology Development

and Commercialization Branch, National

Cancer Institute, National Institutes of Health.

Dated: April 30, 1998.

Jack Spiegel,

Director, Division of Technology Development

and Transfer, Office of Technology Transfer,

National Institutes of Health.

[FR Doc. 98–16427 Filed 6–19–98; 8:45 am]

BILLING CODE 4140–01–M

DEPARTMENT OF HEALTH AND

HUMAN SERVICES

National Institutes of Health

Licensing Opportunity and/or

Cooperative Research and

Development Agreement (‘‘CRADA’’)

Opportunity: Drug and Method for the

Therapeutic Treatment of Ovarian

Cancer and Mesotheliomas

AGENCY: National Institutes of Health,

PHS, DHHS.

ACTION: Notice.

SUMMARY: The NIH is a seeking

Licensee(s) and/or Cooperative Research

and Development Agreement

(‘‘CRADA’’) Collaborators to further

develop, evaluate, and commercialize a

recombinant immunotoxin, termed

SS(dsFv)–PE38. SS(dsFv)–PE38 is a

disulfide-linked recombinant

immunotoxin fused to PE38, a mutant

form of Pseudomonas Exotoxin, that

binds to mesothelin. Mesothelin is a

differentiation antigen present on the

surface of most ovarian cancers,

mesoltheliomas, and several other types

of human cancers including cervical

cancer. In normal tissue, mesothelin is

limited in its expression to mesothelial

cells and basal cells of the trachea (low

expression). Therefore, it represents an

excellent target for antibody-mediated

delivery of cytotoxic agents. The antigen

is a 40 kD glycoprotein that is attached

to the cell surface by

phosphatidylinositol. SS (dsFv)–PE38

immunotoxin is very cytotoxic to cancer

cells expressing mesothelin and binds

with an affinity of approximately 11

nanomolar. The SS (dsFv)–PE38

immunotoxin also produces complete

regressions of mesothelin containing

solid tumors growing in nude mice. The

goal is to move this drug and

methodology into clinical trials. The

invention is claimed in USPA SN 08/

776,271 and PCT patent application

PCT/US97/00224, entitled: ‘‘Mesothelin,

A Differentiation Antigen Present on

Mesothelium, Mesotheliomas and

Ovarian Cancers and Methods and Kits

for targeting the Antigen’’ and is

available for either exclusive or nonexclusive licensing (in accordance with

35 U.S.C. 207 and 37 CFR Part 404).

DATES: Respondees interested in

licensing the invention(s) will be

required to submit an ‘‘Application for

License to Public Health Service

Inventions’’ on or before September 21,

1998 for priority consideration.

Interested CRADA Collaborators must

submit a confidential proposal summary

to the NCI on or before September 21,

1998 for consideration. Guidelines for

preparing full CRADA proposals will be

communicated shortly thereafter to all

respondents with whom initial

confidential discussions will have

established sufficient mutual interest.

CRADA proposals submitted thereafter

may be considered if a suitable CRADA

Collaborator has not been selected.

ADDRESSES: Questions about licensing

opportunities may be addressed to J.R.

Dixon, Ph.D., Technology Licensing

Specialist, Office of Technology

Transfer, National Institutes of Health,

6011 Executive Boulevard, Suite 325,

Rockville, Maryland 20852–3804;

Telephone: (301) 496–7056 ext. 206;

Facsimile: (301) 402–0220; E-Mail:

‘‘DixonJOD.NIH.GOV’’. Information

about Patent Applications and pertinent

information not yet publicly described

can be obtained under the terms of a

Confidential Disclosure Agreement.

Respondees interested in licensing the

invention(s) will be required to submit

an ‘‘Application for License to Public

Health Service Inventions’’.

Depending upon the mutual interests

of the Licensee(s) and the National

Cancer Institute (‘‘NCI’’), a Cooperative

Research and Development Agreement

(CRADA) to collaborate to improve the

properties of the SS(dsFv)–PE38

immunotoxin may also be negotiated.

Proposals and questions about this

CRADA opportunity may be addressed

to Ms. Karen Maurey, Acting Deputy

Director, National Cancer Institute,

Technology Development &

Commercialization Branch, 6120

Executive Plaza South-Room 450,

Rockville, Maryland 20852; Telephone:

(301) 496–0477; Facsimile: (301) 402–

2117. Respondees interested in

submitting a CRADA proposal should be

aware that it may be necessary to secure

a license to the above mentioned patent

rights in order to commercialize

products arising from a CRADA.

SUPPLEMENTARY INFORMATION: NIH/NCI

scientists have done toxicity studies

with the SS(dsFv)-PE38 immunotoxin in

mice and with an earlier single chain

variant (SSFv-PE38) in Cynomolgus

monkeys. Treatment of mice with 5μg